| Objective:As we know, both genetic background and environmental factors involve in development of type2diabetes (T2DM).The main pathophysiological changes in T2DM are impaired insulin secretion and insulin resistence, so genes which involve in insulin secretion or insulin signaling are important candidate genes for T2DM. We explore the association of SNPs in KCNQl and IDE with beta cell function as well as insulin sensitivity in Tianjin Han population.Methods:We screened600subjects with OGTT,including300cases with T2DM,200cases with impaired glucose regulation (IGR) and100cases with normal glucose tolerance(NGT).After an overnight fasting, all subjects’venous blood was drawn for DNA extraction and measurement of biochemistry parameters. With PCR-RFLP and DNA sequencing, we detected the KCNQ1gene rs231362and IDE genes rs7078413polymorphism in all subjects. Insulin resistance (IR) was estimated according to HOMA-IR and ISI.(3cell function was measured according to HOMA-β, MBCI,△I30/△G30and area under curve of insulin(AUC1),and deposition index(DI30,DI-HOMA) were also measured. Statistical analysis was done in SPSS17.0software.Results:(1)The genotype distribution of KCNQ1rs231362and IDE rs7078413met Hardy-Weinberg principal.(2)HOMA-β、△I30/△G30and AUC1decreased gradually in NGT、IGR、T2DM groups, HOMA-IR increased and ISI decreased gradually in the three groups, the difference had statistic value(P<0.05).(2) Frequencies of CC,CT and TT genotype of KCNQ1rs231362were30%,53%,17%in NGT group,36%,42.5%,21.5%in IGR group,and44%,42.7%,13.3%in T2DM group respectively. Frequencies of risk allele C in NGT, IGR and T2DM group were56.5%,57.25%and65.3%respectively.There was significant difference in genotype and allele distribution between T2DM and NGT or IGR group (P<0.05). The diabetes risk for KCNQl rs231362C allele carrier was1.88fold of the T allele carrier.β cell function(HOMA-β,△I30/△G30, AUC1) and deposition index(DI30, DI-HOMA) gradually decreased in CC,CT and TTgenotype(P<0.05). We failed to find significant difference in IR among three genotypes (P>0.05).(3)Frequencies of AA,AC and CC genotype of IDE rs7078413were24.0%,56.0%,20.0%in NGT group,33.5%.45.5%,21.0%in IGR group,and43.4%,37.3%,19.3%in T2DM group respectively. Frequencies of risk allele A in NGT, IGR and T2DM group were52.0%,56.25%and62.0%respectively. There was significant difference in genotype and allele distribution between T2DM and NGT (P<0.05). The diabetes risk for IDE rs7078413T allele carrier was2.24fold of the A allele carrier. HOMA-IR was higher in AA genotype than CC genotype, the difference had statistic value (P<0.05). ISI was lower in AA genotype than CC genotype, the difference had statistic value (P<0.05). Deposition index (DI30) gradually decreased in CC, AC and AA genotype (P<0.05). We failed to find significant difference in β cell function among three genotypes (P>0.05).(4) Logistic regression showed that KCNQ1rs231362CC genotype(OR=2.418,95%CI:1.334-3.682,P=0.026) and C allele(OR=1.523,95%CI:1.078-3.824,P=0.031), IDE rs7078413AA genotype (OR=2.52695%CI:1.226-4.176, P=0.014) and A allele(OR=1.712,95%CI:1.067-2.436,P=0.004), TG, TC were independent risk factors for T2DM;HOMA-β was protective factors.Conclusion:(DKCNQ1rs231362and IDE rs7078413polymorphisms existed in Tianjin Han population.(2)The polymorphism of KCNQ1gene was highly associated with impaired beta cell function, the decrease of insulin secretion, which is not associated with insulin resistance. The polymorphism of IDE gene was associated with insulin resistance.We confirmed that KCNQ1and IDE genes were the diabetes susceptibility genes.(3) KCNQ1and IDE variations, TC and TG were independent risk factors for diabetes, while HOMA-p was the protective factor. |
PDF Full Text Request